title: Enhanced cytosolic drug delivery using fully biodegradable poly(amino oxalate) particles.
abstract: Rapid endosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially proteins that are susceptible to lysosomal degradation. In this paper, we report poly(amino oxalate) (PAOX) as a new protein delivery system that is capable of disrupting endosomes and mediating cytosolic drug delivery. A cationic fully-biodegradable PAOX was synthesized from a one-step reaction of oxalyl chloride, cyclohexanedimethanol and piperazinediethanol. The incorporation of tertiary amine groups in the backbone of PAOX enhanced its hydrolytic nature, which results in a fast drug release. The studies of confocal fluorescence imaging using calcein and LysoTracker Red revealed that PAOX particles disrupted endosomes via "proton sponge" effects and mediated the cytosolic delivery of membrane-impermeable calcein. A protein delivery efficiency of PAOX particles was evaluated using catalase as a model protein. Catalase-loaded PAOX microparticles significantly inhibited hydrogen peroxide generation in Phorbol-12-myristate-13-acetate (PMA)-stimulated macrophages, in a dose-dependent manner. Given the excellent biocompatibility and physicochemical properties, we anticipate that PAOX is a promising cytosolic protein delivery system and is useful for the treatment of acute inflammatory diseases.
authors.affiliation: Polymer Fusion Research Center, Department of Polymer·Nano Science and Technology, Chonbuk National University, Dukjin, Jeonju 561-756, Republic of Korea.
authors.forename: Kyeongyeol
authors.initials: K
authors.lastname: Seong
authors.forename: Hansol
authors.initials: H
authors.lastname: Seo
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Ahn
authors.forename: Donghyuck
authors.initials: D
authors.lastname: Yoo
authors.forename: Sujin
authors.initials: S
authors.lastname: Cho
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000378:metabolism; D002374:Catalase / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010070:Oxalates / Q000138:chemical synthesis / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism*; D011091:Polyesters / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D010070:Oxalates; D010879:Piperazines; D011091:Polyesters; D006861:Hydrogen Peroxide; D002374:Catalase